Abstract
Neuroactive steroids can be synthetic or endogenous molecules produced by neuronal and glial cells, and peripheral glands. Examples include estrogens, testosterone, progesterone and its reduced metabolites such as 5-dihydroprogesterone and allopregnanolone. Steroids produced by neurons and glia target the nervous system and are called neurosteroids. Progesterone and analog molecules, known as progestogens, have been shown to exhibit neurotrophic, neuroprotective, antioxidant, anti-inflammatory, glial modulatory, promyelinating and remyelinating effects in several experimental models of neurodegenerative and injury conditions. Pleiotropic mechanisms of progestogens may act synergistically to prevent neuron degeneration, astrocyte and microglial reactivity, reducing morbidity and mortality. The aim of this review is to summarize the significant findings related to the actions of progesterone and other progestogens in experimental models and epidemiological and clinical trials of some of the most prevalent and debilitating chronic neurodegenerative disorders, namely Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and Amyotrophic Lateral Sclerosis. We evaluated progestogen alterations presented under pathological conditions, how pathology modifies their levels, as well as the intracellular mechanisms and glial interactions underlying their neuroprotective effects. Furthermore, an analysis of the potential utility of natural progestogens and synthetic progestins as neuroprotective and regenerative agents, when administered exogenously as hormone replacement therapy in menopause, is also discussed.
S. Karger AG, Basel
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